Interleukin-31 in Respiratory Type 2 Inflammatory Diseases: Mechanistic Insights and Therapeutic Potential

Respiratory type 2 inflammatory diseases, including asthma and allergic rhinitis (AR), and chronic rhinosinusitis with nasal polyps (CRSwNP), are characterized by epithelial dysfunction, immune dysregulation, and chronic airway inflammation. Interleukin-31 (IL-31), primarily produced by Th2 cells and other immune and structural cells, has emerged as a pivotal mediator in these conditions. By activating the JAK/STAT and MAPK signaling, IL-31 drives chemokine release, eosinophil recruitment, mucus hypersecretion, and neuroimmune responses. Clinical studies demonstrate that IL-31 levels are elevated and correlate with disease severity, positioning IL-31 as a promising biomarker for diagnosis, prognosis, and treatment response monitoring. Importantly, IL-31 uniquely links type 2 inflammation with sensory nerve dysfunction, addressing unmet clinical needs not fully resolved by conventional IL-4/IL-5-targeted therapies. In this review, we synthesize current mechanistic and clinical evidence on IL-31 in asthma, AR, and CRSwNP, highlight its distinct value compared with other cytokines, and outline the major challenges and research questions that remain unanswered. We further discuss potential translational strategies, including biomarker development and IL-31-targeted interventions, which may provide new opportunities for precision medicine in respiratory type 2 inflammatory diseases.